Abstract
The prognosis of advanced oral squamous cell carcinoma (OSCC) patients remains dismal, and a better understanding of the underlying mechanisms is critical for identifying effective targets with therapeutic potential to improve the survival of patients with OSCC. This study aims to clarify the clinical and biological significance of metastasis-associated long non-coding RNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in OSCC. We found that MALAT1 is overexpressed in OSCC tissues compared to normal oral mucosa by real-time PCR. MALAT1 served as a new prognostic factor in OSCC patients. When knockdown by small interfering RNA (siRNA) in OSCC cell lines TSCCA and Tca8113, MALAT1 was shown to be required for maintaining epithelial-mesenchymal transition (EMT) mediated cell migration and invasion. Western blot and immunofluorescence staining showed that MALAT1 knockdown significantly suppressed N-cadherin and Vimentin expression but induced E-cadherin expression in vitro. Meanwhile, both nucleus and cytoplasm levels of β-catenin and NF-κB were attenuated, while elevated MALAT1 level triggered the expression of β-catenin and NF-κB. More importantly, targeting MALAT1 inhibited TSCCA cell-induced xenograft tumor growth in vivo. Therefore, these findings provide mechanistic insight into the role of MALAT1 in regulating OSCC metastasis, suggesting that MALAT1 is an important prognostic factor and therapeutic target for OSCC.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent tumors in the world with over 500,000 cases diagnosed annually
Since β -catenin and NF-κ B pathways were reported to be the key regulators in Epithelial-mesenchymal transition (EMT), we explored whether Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) gain- or loss- of function could mediate EMT in oral squamous cell carcinoma (OSCC) through β -catenin and NF-κ B pathway
We used measured western blot to evaluated the changes of EMT markers expression in Hep-2 cell with pCDNA-NC or pCDNA-MALAT1 transfection, The results shown that N-cadherin, Vimentin, Slug, MMP-9 and VEGF expression were all upregulated significantly (P < 0.05, Supplementary Figure 1e).These data suggested that MALAT1 might involve in regulating β -catenin and NF-κ B signaling pathways in OSCC
Summary
Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent tumors in the world with over 500,000 cases diagnosed annually. Epithelial-mesenchymal transition (EMT) endows metastatic properties upon cancer cells to promote migration, invasion, and subsequent dissemination and it is mainly characterized by loss of E-cadherin expression[3,4]. Up to now, it is unclear which subpopulation of OSCC patients will develop lymphnode or distant metastasis. Mechanistic investigations showed that MALAT1 was transcriptionally activated by c-Fos or Sp1 in renal cell carcinoma and lung cancer cells[15,16]. By using gain- or lose-of-function assays, we validated that MALAT1 contributed to EMT-mediated metastasis in OSCC by modulating the activation of β -catenin and NF-κ B pathways
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